1. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial
- Author
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Kohei Shitara, Mustafa Özgüroğlu, Yung-Jue Bang, Maria Di Bartolomeo, Mario Mandalà, Min-Hee Ryu, Lorenzo Fornaro, Tomasz Olesiński, Christian Caglevic, Hyun C Chung, Kei Muro, Eray Goekkurt, Wasat Mansoor, Raymond S McDermott, Einat Shacham-Shmueli, Xinqun Chen, Carlos Mayo, S Peter Kang, Atsushi Ohtsu, Charles S Fuchs, Guillermo Lerzo, Juan Manuel O'Connor, Guillermo Ariel Mendez, James Lynam, Niall Tebbutt, Mark Wong, Andrew Strickland, Chris Karapetis, David Goldstein, Paul Vasey, Jean-Luc Van Laethem, Eric Van Cutsem, Scott Berry, Mark Vincent, Bettina Muller, Felipe Rey, Angela Zambrano, Joaquin Guerra, Merete Krogh, Lene Baeksgaard, Mette Yilmaz, Anneli Elme, Andrus Magi, Paivi Auvinen, Tuomo Alanko, Markus Moehler, Volker Kunzmann, Thomas Seufferlein, Peter Thuss-Patience, Thomas Hoehler, Georg Haag, Salah-Eddin Al-Batran, Hugo Castro, Karla Lopez, Mynor Aguilar Vasquez, Mario Sandoval, Ka On Lam, Sinead Cuffe, Cathy Kelly, Ravit Geva, Ayala Hubert, Alex Beny, Baruch Brenner, Aprile Giuseppe, Alfredo Falcone, Evaristo Maiello, Rodolfo Passalacqua, Vincenzo Montesarchio, Hiroki Hara, Keisho Chin, Tomohiro Nishina, Yoshito Komatsu, Nozumo Machida, Shuichi Hironaka, Taroh Satoh, Takao Tamura, Naotaoshi Sugimoto, Haruhiko Cho, Yashushi Omuro, Ken Kato, Masahiro Goto, Ichinosuke Hyodo, Kazuhiro Yoshida, Hideo Baba, Taito Esaki, Junji Furuse, Wan Zamaniah Wan Mohammed, Carlos Hernandez Hernandez, Juan Casas Garcia, Adriana Dominguez Andrade, Katriona Clarke, Geir Hjortland, Nils Glenjen, Tomasz Kubiatowski, Jassem Jacek, Marek Wojtukiewicz, Sergey Lazarev, Yuri Lancukhay, Sergey Afanasayev, Vladimir Moiseyenko, Vladimir Kostorov, Svetlana Protsenko, Vadim Shirinkin, Dina Sakaeva, Natalia Fadeeva, Wei Peng Yong, Chau Hsien Matthew Ng, Barbara Robertson, Bernardo Rapaport, Graham Cohen, Lydia Dreosti, Paul Ruff, Conrad Jacobs, Gregory Landers, Waldemar Szpak, Sang-Young Roh, Jeeyun Lee, Yeul Hong Kim, Hyun Cheol Chung, Maria Alsina Maqueda, Federico Longo Munoz, Andres Cervantes Aguilar, Enrique Aranda Aguilar, Pilar Garcia Alfonso, Fernando Rivera, Jaime Feliu Batle, Roberto Pazo Cid, Kun-Huei Yeh, Jen-Shi Chen, Yee Chao, Chia-Jui Yen, Oguz Kara, Suayib Yalcin, Daniel Hochhauser, Ian Chau, Al Benson, Veena Shankaran, Walid Shaib, Philip Philip, Vivek Sharma, Robert Siegel, Weijing Sun, Zev Wainberg, Ben George, Andrea Bullock, Samuel Myrick, Josephine Faruol, Richard Siegel, Timothy Larson, Carlos Becerra, Suresh Ratnam, Donald A. Richards, and Stephen L. Riche
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Male ,0301 basic medicine ,medicine.medical_specialty ,Esophageal Neoplasms ,Paclitaxel ,medicine.medical_treatment ,Population ,Phases of clinical research ,Pembrolizumab ,Adenocarcinoma ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,medicine ,Humans ,Infusions, Intravenous ,education ,Survival rate ,Aged ,Neoplasm Staging ,education.field_of_study ,Chemotherapy ,business.industry ,Hazard ratio ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Survival Rate ,Treatment Outcome ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Female ,Esophagogastric Junction ,business - Abstract
Summary Background Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Methods This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. Eligible patients were randomised (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel. Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher. Safety was assessed in all patients, irrespective of CPS. The significance threshold for overall survival was p=0·0135 (one-sided). This trial is registered at ClinicalTrials.gov, number NCT02370498. Findings Between June 4, 2015, and July 26, 2016, 592 patients were enrolled. Of the 395 patients who had a PD-L1 CPS of 1 or higher, 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel. As of Oct 26, 2017, 326 patients in the population with CPS of 1 or higher had died (151 [77%] of 196 patients in the pembrolizumab group and 175 [88%] of 199 patients in the paclitaxel group). Median overall survival was 9·1 months (95% CI 6·2–10·7) with pembrolizumab and 8·3 months (7·6–9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66–1·03; one-sided p=0·0421). Median progression-free survival was 1·5 months (95% CI 1·4–2·0) with pembrolizumab and 4·1 months (3·1–4·2) with paclitaxel (HR 1·27, 95% CI 1·03–1·57). In the total population, grade 3–5 treatment-related adverse events occurred in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel. Interpretation Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher. Pembrolizumab had a better safety profile than paclitaxel. Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing. Funding Merck Sharp & Dohme, a subsidiary of Merck & Co.
- Published
- 2018